Amantadine Hydrochloride Capsules
DEFINITION
Amantadine Hydrochloride Capsules contain NLT 95.0% and NMT 105.0% of the labeled amount of amantadine hydrochloride (C10H17N·HCl).
IDENTIFICATION
• Infrared Absorption 
197S
197S
Cell:
1 mm
Sample solution:
Place the contents of Capsules, equivalent to 200 mg of amantadine hydrochloride, in a vessel, dissolve in 0.1 N hydrochloric acid, and filter. Transfer the filtrate to a separator, add 1 mL of 5 N sodium hydroxide, and extract with 5 mL of methylene chloride. Filter the extract through anhydrous sodium sulfate, and rinse the anhydrous sodium sulfate with 2 mL of methylene chloride.
ASSAY
• Procedure
Internal standard solution:
0.4 mg/mL of naphthalene in hexane
Standard stock solution:
2 mg/mL of USP Amantadine Hydrochloride RS in water
Standard solution:
Pipet 25.0 mL of Standard stock solution into a 250-mL separator, and add 25 mL of 2.0 N sodium hydroxide and 50.0 mL of Internal standard solution. Shake for 60 min, and collect the hexane layer (Standard solution).
Sample solution:
Transfer NLT 20 Capsules to a 200-mL volumetric flask. Add 40 mL of 0.1 N hydrochloric acid, and heat gently to achieve complete dissolution. Cool, and dilute with water to volume. Pipet 5.0 mL of the solution into a 250-mL separator, and add 40 mL of 1.0 N sodium hydroxide and 50.0 mL of Internal standard solution. Shake for 60 min, and collect the hexane layer (Sample solution).
Chromatographic system
Mode:
GC
Detector:
Flame ionization
Column:
2-mm × 1.22-m; glass column packed with 10% phase G1 on 100- to 120-mesh support S1A
Temperature
Column:
115
Injector:
250
Detector block:
250
Injection size:
1 µL
System suitability
Sample:
Standard solution
Suitability requirements
Resolution:
NLT 2 between napthalene and amantadine
Tailing factor:
NMT 2.0 for the analyte peak
Relative standard deviation:
NMT 2.0%
Analysis
Samples:
Standard solution and Sample solution
Calculate the percentage of C10H17N·HCl in the portion taken:
Result = (RU/RS) × (CS/CU) × 100
| RU | = | = peak response ratios from the Sample solution |
| RS | = | = peak response ratios from the Standard solution |
| CS | = | = concentration of USP Amantadine Hydrochloride RS in the Standard solution (mg/mL) |
| CU | = | = nominal concentration of the Sample solution (mg/mL) |
Acceptance criteria:
95.0%–105.0%
PERFORMANCE TESTS
• Dissolution 711
711
Test 1:
Procedure for a Pooled Sample
Medium:
Water; 900 mL
Apparatus 1:
100 rpm
Time:
45 min
Internal standard solution:
0.054 mg/mL of naphthalene in hexane
Standard stock solution:
0.1 mg/mL of USP Amantadine Hydrochloride RS in water
Standard solution:
Pipet 15.0 mL of Standard stock solution into a 50-mL screw-capped test tube, add 5.0 mL of 5 N sodium hydroxide and 10.0 mL of Internal standard solution, and shake for 60 min. Collect the hexane layer.
Sample solution:
Filter 15.0 mL of the solution under test, and place into a 50-mL screw-capped test tube. Pipet 5.0 mL of 5 N sodium hydroxide and 10.0 mL of the Internal standard solution into the test tube, and shake for 60 min. Collect the hexane layer (Sample solution).
Chromatographic system:
Proceed as directed in the Assay.
Injection size:
2.5 µL
Analysis
Samples:
Standard solution and Sample solution
Tolerances:
NLT 75% (Q) of the labeled amount of C10H17N·HCl is dissolved.
Test 2:
If the product complies with this test, the labeling indicates that it meets USP Dissolution Test 2.
Medium:
Water; 900 mL
Apparatus 2:
75 rpm, with sinkers. [Note—A suitable sinker is available as catalog number CAPWHT-2S from www.qla-llc.com or www.tabletdissolution.com or www.labhut.com. ]
Time:
45 min
Internal standard solution:
0.06 mg/mL of naphthalene in hexanes
Standard stock solution:
0.12 mg/mL of USP Amantadine Hydrochloride RS in Medium
Standard solution:
Transfer 60.0 mL of the Standard stock solution to a 200-mL volumetric flask. Add 20 mL of 5 N sodium hydroxide and 40.0 mL of Internal standard solution. Shake the flask for approximately 10 min, and allow the layers to separate. Use the top layer for injection. The final concentration is about 0.18 mg/mL.
Sample solution:
Transfer 3.0 mL of the solution under test to a centrifuge tube. Add 1.0 mL of 5 N sodium hydroxide and 2.0 mL of Internal standard solution. Shake the tube for approximately 10 min, and allow the layers to separate. Use the top layer for injection.
Chromatographic system
Mode:
GC
Detector:
Flame ionization
Column:
0.32-mm × 30-cm, 0.25-µm film, phase G1
Temperature
Oven:
100 for 3 min, to 200 at 10/min, held at 200 for 2 min
for 3 min, to 200 at 10/min, held at 200 for 2 min
Injector:
250
Detector:
300
Carrier gas:
Helium, 1.4 mL/min
Flow rate:
20 mL/min
Injection size:
2 µL
System suitability
Sample:
Standard solution
Suitability requirements
Resolution:
NLT 2 between naphthalene and amantadine hydrochloride
Tailing factor:
NMT 2.0 for amantadine hydrochloride
Relative standard deviation:
NMT 2.0%
Analysis
Samples:
Standard solution and Sample solution
Calculate the percentage of amantadine hydrochloride released:
Result = (RU/RS) × (CS/L) × V × 100
| RU | = | = ratio of the peak areas from the Sample solution |
| RS | = | = average ratio of the peak areas from the Standard solution |
| CS | = | = concentration of amantadine hydrochloride in the Standard stock solution (mg/mL) |
| L | = | = label claim (mg/capsule) |
| V | = | = volume of Medium, 900 mL |
Tolerances:
NLT 75% (Q) of the labeled amount of amantadine hydrochloride is dissolved.
• Uniformity of Dosage Units 905:
Meet the requirements
905:
Meet the requirements
ADDITIONAL REQUIREMENTS
• Packaging and Storage:
Preserve in tight containers.
• Labeling:
When more than one Dissolution test is given, the labeling states the Dissolution test used only if Test 1 is not used.
• USP Reference Standards 11
11
USP Amantadine Hydrochloride RS 
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Auxiliary Information—
Please check for your question in the FAQs before contacting USP.
| Topic/Question | Contact | Expert Committee |
|---|---|---|
| Monograph | Behnam Davani, Ph.D., M.B.A.
Senior Scientific Liaison 1-301-816-8394 |
(SM12010) Monographs - Small Molecules 1 |
| 711 |
Margareth R.C. Marques, Ph.D.
Senior Scientific Liaison 1-301-816-8106 |
(GCDF2010) General Chapters - Dosage Forms |
| Reference Standards | RS Technical Services 1-301-816-8129 rstech@usp.org |
USP35–NF30 Page 2153
Pharmacopeial Forum: Volume No. 35(1) Page 61